The broad goal of this proposal is to uncover neural mechanisms underlying sensorimotor integration. This goal will be addressed by investigating the neural circuitry that controls a finely coordinated and goal- directed zebrafish behavior, the capture of prey. Zebrafish are an emerging model for systems neuroscience and possess several significant experimental advantages, the combination of which is unparalleled in any other vertebrate system-. These advantages include powerful genetics, transparency for optophysiology, and a diverse behavioral repertoire that develops within a week of fertilization. Larval zebrafish use a series of low angle turns and tracking swims to orient toward and ultimately strike at their prey. This behavior is visually guided and relies heavily on high-order sensory processing by the optic tectum. The focus of this proposal is to define the role of identified reticulospinal neurons that have been implicated in prey capture. These neurons reside in the midbrain nucleus of the medial longitudinal fasciculus (nMLF), the teleost equivalent to the mammalian midbrain premotor region. Neurons in the nMLF receive direct input from the optic tectum and have projections that innervate spinal circuits;placing nMLF neurons at the intersection of sensory and motor systems involved in prey capture. The Aims in this proposal are designed to test specific hypotheses about how distinct neural subpopulations in the nMLF translate sensory information into motor output during the different components of prey capture. These hypotheses will be tested using a combination of behavioral analyses, in vivo calcium imaging and newly developed genetic approaches for activating and silencing discrete brain regions. The research is significant because it will advance our knowledge of a goal-directed vertebrate behavior, the mechanisms of which are poorly understood. The research is also likely to establish methodologies for characterizing other neural circuits in zebrafish. PUBLIC HEALTH RELEVANCE: Mapping neural circuits involved in behavior provides a framework in which to understand how genes and environmental factors that underlie neurological diseases produce their behavioral effects. Given the high degree of conservation across vertebrates, circuit mapping coupled with the vast pool of genetic data and tools in zebrafish should provide a powerful combination for gaining insights into human neurological diseases.